Breast CancerPhase 2NCT01952054
Denosumab for Breast Cancer With Bone Mets
A Phase 2 study testing Denosumab in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if denosumab in combination with a hormonal drug can help lower the number of circulating tumor cells (CTCs) in patients with breast cancer that has spread to the bone. The safety of this combination will also be studied. This is an investigational study. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Denosumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Feb 2015to 10 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients have histological confirmation of breast carcinoma.
- Patients have progressive metastatic disease with predominantly bone metastasis with 1 or more lesions and at least 1 bone lesion has pathological confirmation, have not been treated or have been treated with any prior therapies (including bisphosphonate treatment and/or radiation therapy). Patients can have soft tissue involvement (Lymph node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc).
- Patients have positive ER expression in the primary tumor site by IHC (defined as >/=10%) (PR status is not required)
- Adequate hematologic function: 1)Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L, 2) Platelet count >/= 50 x 10^9/L, 3) Hemoglobin >/= 9.0 g/dL
- Adequate cardiac function (LVEF >/= 45%) if patient has known cardiac dysfunction history
- Adequate Renal function: Calculated creatinine clearance >30 ml/min
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- Adequate Hepatic function: 1) Aspartate aminotransferase (AST) </= 2.5 x ULN; 2) Alanine aminotransferase (ALT) </= 2.5 x ULN; 3) Alkaline phosphatase (Alp) </= 2.5 x ULN; 4) Total bilirubin </= 2.0 x ULN
- Serum calcium or albumin-adjusted serum calcium >/=2.0mmol/L (8.0mg/dL) and </= 2.9 mmol/L (11.5mg/dL)
- Patients have ability and willingness to sign written informed consent.
- Patients are 18 years of age or older.
- Female patients of childbearing potential (A female not free from menses > 2 years or not surgically sterilized) must be willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study. Highly effective contraception, defined as male condom with spermicide, diaphragm with spermicide, intra-uterine device. Highly effective contraception must be used by both sexes during the study and must be continued for 5 months after the last dose of denosumab.
- Female patients of childbearing potential must have negative serum pregnancy test </= 21 days prior to starting study treatment.
- Patients have CTC >/=3.
Who cannot join
- Patients have known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D).
- Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy and biological therapy) while taking study medication. However, patients receiving CDK4/6 inhibitor or mTOR inhibitor as a standard of care while on study is permitted.
- Patients with metastatic sites that requires chemotherapy.
- Patients with active infection and requiring IV or oral antibiotics.
- Patients with concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety.
- Patients have HER2-positive breast carcinoma (IHC staining more than 3+ or HER2 gene amplification by FISH)
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- Patient is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment.
- Patient is of child bearing potential and is not willing to use, in combination with her partner, two highly effective methods of contraception or abstinence during treatment and for 5 months after the end of treatment.
- Male patients.
- Patients have prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.
- Patients have active dental or jaw condition which requires oral surgery, including tooth extraction.
- Patients have non healed dental/oral surgery, including tooth extraction.
- Patients planned invasive dental procedures.
- Patients experiencing a visceral crisis including severe organ dysfunction as assessed by > Gr 2 symptomatic toxicities, laboratory studies, and/ or rapid progression of disease originating from visceral metastasis.
- Patients that have received the study medication (Xgeva/Prolia).
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Phase II Study of Denosumab to Define the Role of Bone Related Biomarkers in Breast Cancer Bone Metastasis
The goal of this clinical research study is to learn if denosumab in combination with a hormonal drug can help lower the number of circulating tumor cells (CTCs) in patients with breast cancer that has spread to the bone. The safety of this combination will also be studied.
This is an investigational study. Denosumab is FDA approved and commercially available to prevent bone-related events caused by breast cancer that has spread to the bone. Using denosumab to lower CTCs in patients with breast cancer that has spread to the bone is investigational.
Read more
You may have the option of continuing denosumab after the study ends.
Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
Read the detailed description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive denosumab through a needle under your skin on Day 1 of each 28-day study cycle.
Starting on Day 1 of week 4, you will also begin taking a hormonal drug. The study doctor will choose the hormonal drug you receive based on your previous hormonal therapy for breast cancer. The study doctor will give you instructions for taking your hormonal drug.
Study Visits:
On Day 1 of week 4:
- You will have a physical exam
- Blood (about 3 tablespoons) will be drawn for routine tests
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune system.
- Urine will be collected to test for a biomarker that is used to measure the rate of bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an MRI to check the status of the disease.
On Day 1 of Cycle 2 and Cycle 3, blood (about 1 teaspoon) will be drawn for routine tests.
Length of Study:
You may receive the denosumab and hormonal therapy combination for up to 13 weeks. You will be taken off study if the disease gets worse or intolerable side effects occur.
End of Study Visit:
After your last dose of the study drug, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune system.
- Urine will be collected to test for a biomarker that is used to measure the rate of bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an MRI to check the status of the disease.
- Conditions
- Breast Cancer
- Being tested
- Denosumab
- Keywords
- Breast cancer, Breast carcinoma, Bone metastasis, Cancer that has spread to the bone, Denosumab, AMG 162, Prolia, Hormonal agent
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DenosumabDrug
Also called AMG 162, Prolia
120 mg subcutaneously on Day 1 of every 28 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Denosumab | Experimental | Participants receive a single subcutaneous (SC) administration of Denosumab 120 mg every 4 weeks (+/- 5days). Starting week 5, in addition to receiving Denosumab every 4 weeks, participants receive a hormonal agent chosen by each physician, excluding the agent that participants received at adjuvant therapy setting. Receives: Drug: Denosumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Effect of Denosumab in Reducing Circulating Tumor Cells (CTCs) Among Breast Cancer Patients With Bone Metastases.
The difference in number of CTCs in 7.5 ml whole blood from baseline to week4. CTC reduction from baseline to week4 is statistically analyzed using the two-sided paired t-test with the significance level of 0.05.
Measured: Baseline, week 4
Secondary outcomes (2)
The Changes of Epithelial-mesenchymal Transition (EMT) in CTCs
The change in Her2, Muc-1, GA733-2 (EpCAM), Twist, Akt, PI3K and ALDH-1 in CTCs after 1 st cycle of treatment with denosumab.
Measured: Baseline, week 4
The Changes in Urine N-telopeptide Level
The collection urine is performed at baseline, at week4 and the end of 3rd cycle (week13) to evaluate the level of N-telopeptide.
Measured: Baseline up to week 13
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2013 (estimated)
- Study start9 Feb 2015
- Primary completion10 Oct 2018
- Study completion10 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
- Investigators
- Naoto Ueno, MD, PHD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01952054
- Sponsor's protocol ID
- 2013-0007
- Other IDs
- NCI-2014-01273
- Status last verified
- Nov 2019
- First submitted
- 20 Sep 2013
- Last updated
- 22 Nov 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Denosumab to Define the Role of Bone Related Biomarkers in Breast Cancer Bone Metastasis
- ClinicalTrials.gov ID
- NCT01952054
- Acronym / sponsor ID
- 2013-0007
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Breast carcinoma, Bone metastasis, Cancer that has spread to the bone, Denosumab, AMG 162, Prolia, Hormonal agent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 7 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 9 Feb 2015 (actual)
- Primary completion
- 10 Oct 2018 (actual)
- Study completion
- 10 Oct 2018 (actual)
- First posted
- 27 Sep 2013 (estimated)
- Results
- Posted 22 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if denosumab in combination with a hormonal drug can help lower the number of circulating tumor cells (CTCs) in patients with breast cancer that has spread to the bone. The safety of this combination will also be studied.
This is an investigational study. Denosumab is FDA approved and commercially available to prevent bone-related events caused by breast cancer that has spread to the bone. Using denosumab to lower CTCs in patients with breast cancer that has spread to the bone is investigational.
You may have the option of continuing denosumab after the study ends.
Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.
Detailed description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will receive denosumab through a needle under your skin on Day 1 of each 28-day study cycle.
Starting on Day 1 of week 4, you will also begin taking a hormonal drug. The study doctor will choose the hormonal drug you receive based on your previous hormonal therapy for breast cancer. The study doctor will give you instructions for taking your hormonal drug.
Study Visits:
On Day 1 of week 4:
- You will have a physical exam
- Blood (about 3 tablespoons) will be drawn for routine tests
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune system.
- Urine will be collected to test for a biomarker that is used to measure the rate of bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an MRI to check the status of the disease.
On Day 1 of Cycle 2 and Cycle 3, blood (about 1 teaspoon) will be drawn for routine tests.
Length of Study:
You may receive the denosumab and hormonal therapy combination for up to 13 weeks. You will be taken off study if the disease gets worse or intolerable side effects occur.
End of Study Visit:
After your last dose of the study drug, the following tests and procedures will be performed:
- You will have a physical exam.
- Blood (about 3 tablespoons) will be drawn for routine tests.
- Blood (about 5 teaspoons) will be drawn for CTC testing and to check your immune system.
- Urine will be collected to test for a biomarker that is used to measure the rate of bone breakdown.
- If the study doctor thinks it is needed, you will have a PET scan, a bone scan, or an MRI to check the status of the disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Denosumab | Experimental | Drug: DenosumabParticipants receive a single subcutaneous (SC) administration of Denosumab 120 mg every 4 weeks (+/- 5days). Starting week 5, in addition to receiving Denosumab every 4 weeks, participants receive a hormonal agent chosen by each physician, excluding the agent that participants received at adjuvant therapy setting. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients have histological confirmation of breast carcinoma.
- Patients have progressive metastatic disease with predominantly bone metastasis with 1 or more lesions and at least 1 bone lesion has pathological confirmation, have not been treated or have been treated with any prior therapies (including bisphosphonate treatment and/or radiation therapy). Patients can have soft tissue involvement (Lymph node and skin) and/or metastatic lesions at major organ sites (i.e. lung, liver, etc).
- Patients have positive ER expression in the primary tumor site by IHC (defined as >/=10%) (PR status is not required)
- Adequate hematologic function: 1)Absolute neutrophil count (ANC) >/= 1.0 x 10^9/L, 2) Platelet count >/= 50 x 10^9/L, 3) Hemoglobin >/= 9.0 g/dL
- Adequate cardiac function (LVEF >/= 45%) if patient has known cardiac dysfunction history
Key exclusion criteria (15 listed)
- Patients have known sensitivity to any of the products to be administered during the study (e.g., mammalian derived products, calcium, or vitamin D).
- Patients receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, radiation therapy and biological therapy) while taking study medication. However, patients receiving CDK4/6 inhibitor or mTOR inhibitor as a standard of care while on study is permitted.
- Patients with metastatic sites that requires chemotherapy.
- Patients with active infection and requiring IV or oral antibiotics.
- Patients with concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DenosumabAlso: AMG 162, Prolia120 mg subcutaneously on Day 1 of every 28 day cycle. | Drug | Denosumab |
Primary outcome
The Effect of Denosumab in Reducing Circulating Tumor Cells (CTCs) Among Breast Cancer Patients With Bone Metastases.
Time frame: Baseline, week 4
The difference in number of CTCs in 7.5 ml whole blood from baseline to week4. CTC reduction from baseline to week4 is statistically analyzed using the two-sided paired t-test with the significance level of 0.05.
2 secondary outcomes
The Changes of Epithelial-mesenchymal Transition (EMT) in CTCs
Time frame: Baseline, week 4
The Changes in Urine N-telopeptide Level
Time frame: Baseline up to week 13
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Naoto Ueno, MD, PHD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Denosumab in people with Breast Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Effect of Denosumab in Reducing Circulating Tumor Cells (CTCs) Among Breast Cancer Patients With Bone Metastases. (time frame: Baseline, week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2019.